Brown fat activation mitigates alcohol-induced liver steatosis and injury in mice

Shen, Hong; Jiang, Lin; Lin, Jiandie D.; Omary, M. Bishr; Rui, Liangyou

doi:10.1172/jci124376

Cited by 43 publications

(43 citation statements)

References 52 publications

(65 reference statements)

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“…Genetic deletion of Ucp1 exacerbates alcohol-induced liver steatosis, injury, inflammation, and fibrosis in mice. 71 It should be noted that alcohol and obesity have synergistic effects on liver injury, since a clinical study has revealed that obese men who drink 15 or more units of alcohol a week have a substantially higher risk of liver-related mortality than subjects with a single disease. 72 , 73 Moreover, adipocyte death itself predominantly induces liver injury and inflammation in a chemokine (C–C motif) receptor 2-positive (CCR2 + ) macrophage-dependent manner and enhances the sensitivity of hepatocytes to lipotoxicity.…”

Section: Immunological Mechanisms Of Aldmentioning

confidence: 99%

Immunological mechanisms and therapeutic targets of fatty liver diseases

et al. 2020

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Alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) are the two major types of chronic liver disease worldwide. Inflammatory processes play key roles in the pathogeneses of fatty liver diseases, and continuous inflammation promotes the progression of alcoholic steatohepatitis (ASH) and nonalcoholic steatohepatitis (NASH). Although both ALD and NAFLD are closely related to inflammation, their respective developmental mechanisms differ to some extent. Here, we review the roles of multiple immunological mechanisms and therapeutic targets related to the inflammation associated with fatty liver diseases and the differences in the progression of ASH and NASH. Multiple cell types in the liver, including macrophages, neutrophils, other immune cell types and hepatocytes, are involved in fatty liver disease inflammation. In addition, microRNAs (miRNAs), extracellular vesicles (EVs), and complement also contribute to the inflammatory process, as does intertissue crosstalk between the liver and the intestine, adipose tissue, and the nervous system. We point out that inflammation also plays important roles in promoting liver repair and controlling bacterial infections. Understanding the complex regulatory process of disrupted homeostasis during the development of fatty liver diseases may lead to the development of improved targeted therapeutic intervention strategies.

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Section: Immunological Mechanisms Of Aldmentioning

confidence: 99%

Immunological mechanisms and therapeutic targets of fatty liver diseases

et al. 2020

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“…Indeed, the influence of alcohol on BAT physiology (e.g., organ mass, thermogenic activity, and lipolysis) has been reported to be inconsistent between studies and thus appears to be contingent on experimental conditions (11). In this issue, Shen et al extensively investigated the influence of BAT thermogenesis on ALD development by utilizing thermoneutral environment and Ucp1-knockout mice (21). For years, it was not explained why Ucp1 ablation failed to cause obesity in mice, as opposed to the observation that genetic obesity was associated with reduced BAT capacity and activity.…”

Section: Role Of Bat In Alcoholic Liver Diseasementioning

confidence: 99%

How does your fat affect your liver when you drink?

Hwang¹,

Gao²

2019

Journal of Clinical Investigation

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“…Lipid metabolism disorder is the early manifestation of ALD, with reversibility. Therefore, early regulation of lipid metabolism has essential significance for ALD treatment (Shen et al., 2019; Yang et al., 2017). Studies have shown that gut microflora is closely related to lipid metabolism (Chu et al., 2019; Le Roy et al., 2013), especially the bidirectional regulation with bile acids.…”

Section: Introductionmentioning

confidence: 99%

Effect of nicotinamide riboside on lipid metabolism and gut microflora‐bile acid axis in alcohol‐exposed mice

Xue

Liu

et al. 2020

Food Science & Nutrition

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Alcoholic liver disease (ALD) is the most common complication of alcohol abuse, while we lack safe and effective treatment for ALD. This study aimed to explore the effects of nicotinamide riboside (NR) on lipid metabolism and gut microflora‐bile acid axis in alcohol‐exposed mice. NR significantly improved liver histopathological damage and abnormal liver function. NR as a provider of nicotinamide adenine dinucleotide (NAD+) increased the NAD+/NADH ratio. Meanwhile, NR inhibited the activation of the protein phosphatase 1 signaling pathway, decreased the liver triglyceride and total bile acid levels, and reduced lipid accumulation. According to the results of gut microflora species analysis, NR intervention changed the microbial community structure at the phylum, family and genus levels, and the species abundances returned to a level similar to these of the normal control group. Besides, the results of high‐performance liquid chromatograph‐mass spectrometry showed that NR intervention resulted in fecal bile acid levels tending to be normal with decreased chenodeoxycholic acid level and increased deoxycholic acid and hyocholic acid levels. Spearman's correlation analysis showed a correlation between gut microflora and bile acids. Therefore, NR supplementation has the potential to prevent ALD, and its mechanism may be related to regulating lipid metabolism disorders and the gut microflora‐bile acid axis.

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Brown fat activation mitigates alcohol-induced liver steatosis and injury in mice

Cited by 43 publications

References 52 publications

Immunological mechanisms and therapeutic targets of fatty liver diseases

Immunological mechanisms and therapeutic targets of fatty liver diseases

How does your fat affect your liver when you drink?

Effect of nicotinamide riboside on lipid metabolism and gut microflora‐bile acid axis in alcohol‐exposed mice

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